A French prospective observational study of the treatment of chronic hepatitis C in drug abusers.

The objective of this prospective, multicenter, observational study was to evaluate healthcare for hepatitis C virus (HCV)-infected drug abusers in France and to determine predictors of successful therapeutic intervention. A total of 170 drug users were recruited from 40 French centers. Three centers recruited 66 participants (38.8%), and one to eight patients each were enrolled from 37 other centers (n=104). A sustained viral response (SVR) was seen in 65 (38.2%) patients. SVR rates were significantly higher in compliant than in non-compliant patients (43.5% versus 23.9%; P=0.019), in patients from high- rather than low-recruiting centers (54.5% versus 27.9%; P<0.001) and in patients receiving Buprenorphine rather than methadone (48.1% versus 21.8%; P=0.001). In patients, who completed both the treatment and follow-up (n=94), SVR rate was 57.4%. Buprenorphine substitution therapy and genotypes 2 or 3 HCV infection were associated with significantly higher rates of SVR (P<0.01, for both comparisons). In conclusion, successful care of hepatitis requires an active treatment policy of every center toward drug addicts. Additional studies are needed to explore the difference in SVR with methadone versus Buprenorphine therapy.

Detection of HBs antigen, DNA polymerase activity, and hepatitis B virus DNA in tears: relevance to hepatitis B transmission by tears.

Hepatitis B surface antigen, DNA polymerase, and hepatitis B virus DNA have been sought in the tears of 72 patients. These markers were detected in a high percentage of hepatitis B carriers, which proves the presence of hepatitis B virus in the tears and raises the question of its eventual transmission in this way. The severity and extreme contagiousness of hepatitis B together with the increasing number of virus carriers justify systematic sanitary rules among ophthalmic clinicians and staff, but vaccination remains the best mean of limiting the spread of the disease.

[Viral replication and hepatic manifestations in 7 cases of periarteritis nodosa associated with hepatitis B virus]. / Etude de la réplication virale et des manifestations hépatiques dans sept cas de périartérite noueuse associés au virus de l'hépatite B.

Viral replication was studied in 7 cases of PAN associated with hepatitis B virus (HBV). Serum and liver were strongly positive for markers reflecting HBV replication (constant high levels of HBe Ag, numerous hepatocytes nuclei reactive for HBc Ag, high DNA-polymerase activity). No cases were found to be positive for delta antigen or antibody. Mild biological and histological signs of liver damage were present in all patients but one. In PAN, high replication might lead to continuous stimulation and formation of circulating immune complexes in antigen excess which deposit in vascular walls with subsequent vasculitis. The demonstration of intense and permanent HBV replication could explain the unsatisfactory results observed with steroids and immunosuppressive drugs. Since steroids have been shown to increase HBV replication, this therapy might contribute to the perpetuation of the immunopathogenic process responsible for PAN. A more rational approach should take advantage of new antiviral drugs inhibiting HBV replication as suggested by preliminary beneficial results.

[Influence of HIV infection on hepatitis B virus infection in homosexual patients]. / Influence de l'infection à VIH sur l'infection par le virus de l'hépatite B chez les patients homosexuels.

Clinical expression and outcome of hepatis B virus infections associated with human immunodeficiency virus infection (without AIDS) were studied in 17 homosexuals during 23 months. In an attempt to distinguish the respective impacts of homosexuality from that of human immuno-deficiency virus, patient were compared with a population of homosexual males infected by hepatitis B virus alone. The ratio of biochemical evidence of liver cell necrosis (ALAT)/viral replication (DNAp) was significatively decreased (p less than 0.01), despite evidence of severe histological damage in some cases. Two-thirds of patients with HBV replication tolerated HBV infection at the end of follow-up. This tolerance was significatively more common than in homosexuals infected by HBV alone (p less than 0.01), and did not appear to be related to decreased T4 cell count but seemed to correlate with the existence of the AIDS related complex.

[Course of the recurrence of hepatitis C virus infection after liver transplantation]. / Evolution de la récidive de l'infection par le virus de l'hépatite C après transplantation hépatique.

OBJECTIVES: Hepatitis C virus recurrence is frequent after orthotopic liver transplantation. The aim of this study was to evaluate the clinical, biological, and histological characteristics of recurrence. METHODS: One hundred and ten patients (91 males, mean age 49 years) with liver transplantation were followed up for more than 1 year (mean: 26 months, range: 12-71). Hepatitis C virus serologic 2nd generation tests were performed before and every 3 months after transplantation in all patients. Serum RNA was detected every 6 months after transplantation by polymerase chain reaction. A percutaneous liver biopsy was performed every year in all patients and in case of abnormal biological liver tests. RESULTS: In 44 patients (40%), hepatitis C virus serology was positive before transplantation, and was unchanged after transplantation. In this group histologic chronic hepatitis was observed in 35 patients (79.5%). The mean Knodell score was 8.4 +/- 2.3, associated with an increase in serum aminotransferases (> twice the upper limit of normal) in 26 cases (74.3%) and with serum RNA in 33 cases (94.3%). The Knodell score was not significantly higher 2 years or more after transplantation than before (9.5 +/- 3.9 vs 7.2 +/- 3.5). In 66 patients with negative hepatitis C virus serology before transplantation, no changes were noted after transplantation. In this group, histologic chronic hepatitis was found in 14 cases (21.2%) associated with serum hepatitis C virus RNA in 7 cases. Actuarial survival rates of the two groups were 97.1% and 91.2% at 2 years, and 93.5% and 86.7% at 5 years, respectively. No death clearly related to hepatitis C virus recurrence was observed. CONCLUSION: Hepatitis C virus recurrence after liver transplantation is frequently associated with chronic hepatitis, and a progressive increase in liver lesions. Nevertheless, the 5-year survival rates was not different in these patients compared to patients with negative hepatitis C virus serology before transplantation.

[Epidemiological information obtained from anti-hepatitis C virus screening in blood donors and candidates for autologous transfusion from 1992 to 1996 in the Alpes-Maritimes region]. / Renseignements épidémiologiques fournis par l'évolution du dépistage des anticorps dirigés contre le virus de l'hépatite C de 1992 à 1996 chez les donneurs de sang et les candidats à une transfusion autologue dans le département des Alpes-Maritimes.

OBJECTIVES: To determine the evolution of the frequency of anti-hepatitis C virus antibodies from 1992 to 1996 in blood donors and in candidates for autologous transfusion in the Alpes-Maritimes region and to assess risk factors. METHODS: Anti-hepatitis C virus antibodies were assessed by second generation ELISA in 1992 and in the first quarter of 1993, and then by third generation ELISA; in all cases, anti-hepatitis C virus antibodies were confirmed by RIBA test. RESULTS: Since 1992 (when the second generation ELISA test became available), the prevalence of anti-hepatitis C virus antibodies in blood donors in the Alpes-Maritimes region (0.54% in 1992 to 0.20% in 1996) has decreased. Positive ELISA anti-hepatitis C virus was confirmed by RIBA in 53 to 68% of anti-hepatitis C virus blood donations. The percentage of anti-hepatitis C virus donors with ALT above the upper limit (donation exclusion threshold) was between 28 and 56%.The most frequent age interval for new anti-hepatitis C virus positive donors was between 30 and 40 years. Since 1992, a third of the anti-hepatitis C virus blood donors agreed to participate in a medical history questionnaire. One or several risk factors were found in almost all donors. The most frequent source of infection was nosocomial (50%). During the 5 years of the study, the number of candidates for autologous transfusion increased: 717 in 1992 to 1 528 in 1996. The prevalence of anti-hepatitis C virus in this older population (mean age: 64 years) decreased progressively (2.9% in 1992 to 1.1% in 1996, P<0, 01) since the prevalence of anti-HBc remained stable, near 12%. Among the 96 subjects found to be anti-hepatitis C virus positive before an autologous transfusion, 49 were transfused before 1990 and 40 had a history of surgery. CONCLUSION: The prevalence of anti-hepatitis C virus has decreased since 1992 in blood donors and in candidates for autologous transfusion which may suggest that there is better screening in the general population and presenting the spread of hepatitis C virus infection.

[Risk of transmission of hepatitis C virus by digestive endoscopy]. / Risque de transmission du virus de l'hépatite C par l'endoscopie digestive.

OBJECTIVE: In 30 to 50% of cases, the route of transmission of virus C remains unknown. The aim of this study was to investigate the effectiveness of manual cleaning and disinfection procedures after endoscopic examinations in highly infected patients. METHODS: In 39 patients with chronic hepatitis C and a high level of replication, a gastroscopy with biopsy was performed with a fully submersible endoscope. Cleaning and disinfection were carried out with the following protocol: cleaning with detergent solution (Sekulyse), rinsing, 3 to 5 min immersion into a glutaraldehyde disinfectant solution (Sekucid) and final rinsing. One hundred mL of sterile water was flushed through the biopsy channel immediately after removal of the endoscope (T1), after cleaning (T2), and after final disinfection (T3). These 100 mL were collected in aliquots for viral and bacterial screening. Virus C particles were searched for in the effluent of the biopsy channel using two methods of polymerase chain reaction. RESULTS: Virus C particles were found in 2 of 39 patients in T1 aliquots collected before washing. Routine cleaning with a detergent eliminated all viral particles, as tests were negative at T2 and T3. The usual bacteria (Pseudomonas, Streptococcus, Neisseria...) were detected at T1 and had disappeared after total disinfection at T3. CONCLUSION: Virus C hepatitis could be transmitted during endoscopic examination, but cleaning and disinfection procedures effectively eliminated all viral particles.

[Hepatic resection and transplantation for hepatocellular carcinoma in patients with cirrhosis]. / Résection et transplantation hépatique pour carcinome hépatocellulaire chez les malades atteints de cirrhose.

OBJECTIVES: Liver resection and liver transplantation are the only curative treatments for hepatocellular carcinoma in patients with cirrhosis. The aim of this retrospective study was to compare survival and tumor recurrence in patients with cirrhosis after hepatic resection or liver transplantation for hepatocellular carcinoma in patients with cirrhosis. METHODS: Between March 1988 and March 1995, 34 patients underwent liver resection and 30 patients with cirrhosis had liver transplantation for hepatocellular carcinoma. The probability of survival and recurrence were studied according to clinical, biological and pathological factors, defined in liver specimens. Comparisons were performed by the actuarial method and log rank test. RESULTS: Five-year survival after resection and transplantation was 13% and 32.6%, respectively, and 5-year recurrence was 92.6% and 40.9%, respectively (P < 0.01). The diameter of nodules was a significant predictive factor of recurrence in resected patients; the number of nodules was a significant predictive factor in transplanted patients. The combination of these two factors could be used to identify two groups: patients with large carcinoma (diameter > 5 cm and/or number of nodules > 3), and patients with small carcinoma (diameter < or = 5 cm and number of nodules < or = 3). The five-year survival rate of large hepatocellular carcinoma was 17.3% after resection and 0% after transplantation. The five-year survival rate of small hepatocellular carcinoma was 0% after resection and 69.3% after transplantation (P < 0.01). The five-year recurrence of large hepatocellular carcinoma was 72.3% after resection and 100% after transplantation. The five-year recurrence of small hepatocellular carcinoma was 82.6% after resection and 11.1% after transplantation (P < 0.01). CONCLUSIONS: Liver transplantation seems to be the best treatment for small hepatocellular carcinoma, mainly because of a lower recurrence rate. On the other hand, both treatments had a high recurrence rate in large hepatocellular carcinoma.

[Recurrence of virus B hepatitis after liver transplantation]. / Récidive du virus de l'hépatite B après transplantation hépatique.

Thirty-three HBs antigen positive patients without signs of viral replication underwent orthotopic liver transplantation and received long term passive immunoprophylaxis with anti-HBs immunoglobulins at high doses perioperatively and then at a dose of 10,000 IU every month. All patients became negative during the first 6 months following surgery. At 34 months the survival rate was 67 percent and the actuarial recurrence rate of serum HBs antigen was 7.1 percent. Reappearance of HBs antigen was associated with evidence of HBV replication and histological alterations of the graft. In our experience, long term passive immunoprophylaxis reduces HBV reinfection of the grafted liver.

[Vidarabine treatment of chronic active hepatitis associated with hepatitis B virus multiplication. A randomized multicenter study]. / Traitement par la vidarabine de l'hépatite chronique active associée à la multiplication du virus de l'hépatite B. Etude multicentrique randomisée.

A randomized controlled study of one course of vidarabin was carried out in 30 patients with HBs Ag, HBe Ag, DNAp, positive chronic active hepatitis: 15 patients were treated with vidarabin given intravenously (15 mg/kg/day for 7 days then 7.5 mg/kg/day for 14 days); the other 15 patients received a placebo for 21 days. During treatment, DNA polymerase activity fell dramatically in 13 treated patients and in no controls (p less than 0.001). Six months after inclusion, ALT normalization was observed in 40 p. 100 of the treated patients and 6 p. 100 of the controls (p less than 0.05), a decrease in inflammatory activity on liver biopsies was observed in 70 p. 100 of the treated patients and 20 p. 100 of the controls (p less than 0.05), a permanent lost of DNA polymerase and of HBe Ag occurred in 33 p. 100 and 13 p. 100 of the treated patients and 20 p. 100 and 7 p. 100 of the controls, respectively. In addition, a second course of vidarabin was administered to the 12 patients who were still HBe Ag positive 6 months after the first course. During the next 6 months, 8 patients lost DNA polymerase and 4 lost HBe Ag. Altogether, the final score of durable inhibition of HBV replication was 11/15 (73 p. 100) within one year. The above results demonstrate that one course of vidarabin can significantly improve ALT and liver inflammatory activity but the effect upon HBV replication is only transient. A second course does however increase efficacy on HBV replication without additional side effects.

[Primary neuroendocrine tumor in the intrahepatic bile ducts: a rare finding in an asymptomatic patient]. / Tumeur neuro-endocrine primitive des voies biliaires intrahépatiques: une découverte exceptionnelle chez un malade asymptomatique.

Neuroendocrine tumors of the biliary tree are rare. In all cases except one, diagnosis was made in symptomatic patients. We report a case of an asymptomatic intrahepatic bile duct neuroendocrine tumor in a 74-year old man. To our knowledge, this is the second reported case of an asymptomatic intrahepatic bile duct neuroendocrine tumor. Diagnosis was only made by anatomopathological examination of the tumor after resection. Systemic and immunohistochemical hormonal screening was negative. Twenty months after surgery, the patient was asymptomatic and there was no recurrence.

[Plasma exchange and acyclovir in Behçet's disease]. / Echanges plasmatiques et acyclovir dans la maladie de Behçet.

It has been postulated that Behçet's disease may be a viral induced vasculitis. In the present study plasma exchanges were applied in an attempt to remove circulating immune complexes and restore cellular immunity. High doses of acyclovir were administered in association with plasma exchanges since it has been shown that herpes simplex virus type 1 might be involved in Behçet's vasculitis. Seven patients with severe ocular manifestations of Behçet's disease were selected for the study. Plasma exchanges were carried out at the rate of 3 per week during 3 weeks and then once every two weeks during 3 months followed by 1 per month during 3 months. 45 mg/day/kg acyclovir were administered intravenously for 21 days. At the end of the follow-up period comparative analysis of panretinal fluorescein angiographies before and after treatment showed no change of the fundus lesions in 3 patients, improvement in only 2 patients and significant worsening in 2 patients. The rather negative results of the present trial lead to assume that HSV-1 is not the virus involved, if any, in Behçet's disease. On the other hand, in the present study, the efficiency of plasma exchanges was transient.

[Risk of transmission of hepatitis C through endoscopy of the digestive tract]. / Risque de transmission du virus de l'hépatite C lors d'une endoscopie digestive.

NOSOCOMIAL TRANSMISSION: Increasingly implicated in HCV infection in patients with no patent risk factors, nosocomial transmission has been demonstrated between patients hospitalized in the same ward and from health carers to patients. The risk of HCV transmission by medical instruments could only be quantified with a prospective study of examined patients. There is a theoretical risk for all endoscopic examinations whatever organ explored. Instrumental manipulations have been found as the only risk factor in blood donors. VALUE OF FORMER DISINFECTION GUIDELINES: Disinfection protocols for endoscopes have been found to eliminate 3 viruses (HCV, HBV, HIV). The endoscope-related risk could be due to minimal bleeding provoked by biopsies (risk factors independent of HCV infection) via the operator channel. THREE REPORTED CASES OF HVC INFECTION: One case of HVC infection following retrograde cholangiography and two after coloscopy have been reported. In all three cases disinfection was found to be insufficient. Recently, an official statement by the French health authorities indicates that a 20-min gluteraldehyde bath is necessary for optimal efficacy. Instruments susceptible to cause bleeding must be sterilized. The sterilization process must be tracable. The anesthesia-related risk appears to be due to use of multidose bottles or reuse of syringes. SAFE ENDOSCOPY: Disinfection procedures must be rigorously applied. One new perspective is the culture of titratable virus models. Several arguments show that well-conducted disinfection of endoscopes and medical instruments can eliminate all risk of viral transmission, including HCV.

[Superiority of a new etiopathogenic treatment curing periarteritis nodosa caused by hepatitis B virus, using a combination of brief corticotherapy, vidarabine and plasma exchange]. / Supériorité d'un nouveau traitement étiopathogénique curateur des périartérites noueuses induites par le virus de l'hépatite B grâce à l'association corticothérapie brève, vidarabine, échanges plasmatiques.

A new physiopathological treatment of HBV-related polyarteritis inspired by advances in the treatment of chronic active hepatitis B was tested in 7 patients. The new protocol included short term corticosteroid therapy, a course of antiviral chemotherapy with vidarabine and repeated plasma exchanges enabling steroids to be discontinued after 2 weeks. This treatment was well tolerated, and 6 of the 7 patients treated were clinically, biologically and virologically cured. The eradication of HBV among the patients who were cured was confirmed by clearance of HBs Ag and its replacement by anti HBs. None of the 6 patients relapsed during a 2 to 7 years' follow-up. The seventh patient died. In contrast, no patient had been cured in a similar group of 7 polyarteritis patients previously treated with the conventional symptomatic therapy using corticosteroids (6/7), plasma exchanges (4/7) and immunosuppressants (2/7). The outcome in this older series followed up for 3 years was altogether unfavourable, with 3 deaths, 3 chronic forms with multiple relapses and 1 spontaneous stabilisation. All patients remained chronic carriers of HBV. These results suggest that the new aetiopathogenic treatment capable of curing polyarteritis patients should replace the classical symptomatic treatment as soon as these preliminary results are confirmed by those of a multicentre study in progress.

[Liver transplantation for hepatocellular carcinoma. Mid-term results]. / Transplantation hépatique pour carcinome hépatocellulaire. Résultats à moyen terme.

The results of liver transplantation for hepatocellular carcinoma are disappointing. Thus, in 11 patients transplanted for hepatocellular carcinoma on cirrhosis, the actuarial survival rate at 3 years was 20 percent, with a postoperative mortality of 27 percent and 4 deaths caused by recurrence of the malignancy. These poor results contrast with those we obtained after liver transplantation for cirrhosis and finding of incidental hepatocellular carcinoma in the resected part of the liver. Out of 6 patients with incidental carcinoma only 1 died postoperatively (16.6 percent), and no case of recurrent malignancy was observed. These results confirm that the malignancy recurrence rate is high after transplantation for large carcinoma. On the other hand, the absence of recurrence after transplantation for incidental hepatocellular carcinoma encourages us to look for small carcinomas on cirrhosis.

[Pretreatment with prednisolone enhances the effect of human lymphoblastoid interferon in chronic hepatitis B]. / Prednisolon-forbehandling øger effekten af humant lymfoblastinterferon ved kronisk hepatitis B. INTERPRED Trial Group.

Patients (n = 213) with chronic hepatitis B were randomised to prednisolone (two weeks of 0.6 mg/kg/day, one week of 0.45 mg/kg/day and one week of 0.25 mg/kg/day) or placebo followed by two weeks rest, and were then given human lymphoblastoid interferon 10 MU daily for five days followed by 10 MU thrice weekly for 11 weeks. There were statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). HBeAg disappearance and HBeAg to anti-HBe seroconversion rates were 28 vs. 44% and 23 vs. 38% (placebo vs. prednisolone). Fifteen patients (7.5%) lost HBsAg. Three out of 22 cirrhotic patients (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome. Prednisolone pre-treatment, enhances the effect of lymphoblastoid interferon in chronic hepatitis B. Interferon treatment (with and without prednisolone) should be used with caution in patients with cirrhosis and avoided in patients with evidence of hepatic decompensation.